Systems and methods for manufacturing and safety of an no2-to-no reactor cartridge used to deliver no for inhalation therapy to a patient

ABSTRACT

The principles and embodiments of the present invention relate to methods and systems for safely providing NO to a recipient for inhalation therapy. There are many potential safety issues that may arise from using a reactor cartridge that converts NO2 to NO, including exhaustion of consumable reactants of the cartridge reactor. Accordingly, various embodiments of the present invention provide systems and methods of determining the remaining useful life of a NO2-to-NO reactor cartridge and/or a breakthrough of NO2, and providing an indication of the remaining useful life and/or breakthrough.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of U.S. patent applicationSer. No. 14/744,298, filed on Jun. 19, 2015, which claims priority under35 USC § 119(e) to U.S. patent application Ser. No. 62/015,088, filedJun. 20, 2014, the entire contents of which are hereby incorporated byreference.

TECHNICAL FIELD

Principles and embodiments of the present invention relate generally tosystems and methods for manufacturing of an NO₂-to-NO reactor cartridgefor delivering NO to a patient, in need thereof, for inhalation therapy,and addressing safety aspects of such manufacturing processes.

BACKGROUND

A number of gases have been shown to have pharmaceutical action inhumans and animals. One such gas is Nitric Oxide (NO) that, wheninhaled, acts to dilate blood vessels in the lungs, improvingoxygenation of the blood and reducing pulmonary hypertension. In thefield of inhalation therapy for various pulmonary conditions such asacute pulmonary vasoconstriction, hypertension and thromboembolism, orinhalation injury, treatment has included the use of the therapeutic gasNO supplied from a gas cylinder. More specifically, this gaseous NO forinhalation therapy is supplied to a patient from a high pressure gascylinder containing NO. For example, such an approach is disclosed inU.S. Pat. No. 5,558,083 entitled “Nitric Oxide Delivery System”, whichis incorporated herein by reference in its entirety.

Unlike supplying NO for inhalation therapy from a high pressure NOcylinder; some have proposed supplying NO for inhalation therapy from asource of Nitrogen Dioxide (NO₂), which is toxic, and converting thistoxic NO₂ into NO using a “cartridge” or “reactor” (NO₂-to-NO reactorcartridge) at the patient's bedside. For example, such an approach isdisclosed in U.S. Pat. No. 8,083,997 (“the '997 Patent”) issued Dec. 27,2011, to Rounbehler et al., and assigned to GENO, LLC, which isincorporated herein by reference in its entirety. The NO₂-to-NO reactorcartridge in the '997 Patent is filled with a loosely packed powder of asurface-active material (e.g., silica) coated with an aqueous solutionof an antioxidant (e.g., aqueous ascorbic acid). Purportedly, thereactor receives NO₂ that passes through the loosely packed silicacoated with the aqueous ascorbic acid and undergoes a chemical reactionthat converts NO₂ to NO, which in turn exits the reactor cartridge andis then delivered to the patient.

Substantial patient safety and efficacy concerns arise from convertingtoxic NO₂ to NO at the patient's bedside as proposed because of at leastthe toxic nature of NO₂. For example, as pointed out in the '997 Patent,“unlike NO, the part per million levels of NO₂ gas is highly toxic ifinhaled and can form nitric and nitrous acid in the lungs.”

Compounding risks relating to such NO₂ to NO conversion at the patient'sbedside, the ability of these NO₂-to-NO reactor cartridges to convertNO₂ to NO exhausts as it uses a consumable reactant and this exhaustionresults in the breakthrough of toxic NO₂, which in turn may be deliveredto the patient. Without an indicator (e.g., dosage meter) to the user ofthe amount of lifetime remaining for the reactor as it exhausts, a userhas no way of confirming how much or little lifetime the reactor hasprior to at least breakthrough of toxic NO₂. This can force the user toguess how much lifetime the reactor has prior to at least breakthroughof toxic NO₂; However, factors impacting the lifetime of the reactorand/or breakthrough of toxic NO₂ may not be readily ascertainable byuser observation.

Further compounding risks relating to such NO₂-to-NO reactor cartridges,the ability of these reactors to convert NO₂ to NO (e.g., lifetime) canbecome compromised resulting in breakthrough of toxic NO₂ beingdelivered to the patient. For example, the reactor can be compromised bya channel that allows NO₂ flow through the reactor cartridge withoutconversion to NO as disclosed in U.S. Pat. No. 8,646,445 (“the '445Patent”) issued Feb. 11, 2014, to Fine et al., and assigned to GENO,LLC, which is incorporated herein by reference in its entirety. Aspointed out in the '445 Patent, “Creation of a channel negates theeffect of the powder and renders the cartridge useless. This problem isso severe that a packed tube like this can only be used if the cartridgeis vertical.”

Another NO₂-to-NO reactor cartridge is discussed in U.S. Pat. No.8,607,785 (“the '785 Patent”) issued Dec. 17, 2013, to Fine et al., andassigned to GENO, LLC, which is incorporated herein by reference in itsentirety. Rather than a loosely packed reactor cartridge, the '785Patent discloses a porous solid structure, which provides a rigidstructure coated with an aqueous solution of an antioxidant. However,such a porous solid structure can be brittle and have its structuralintegrity compromised by sudden shocks or rough handling, as might occurin shipping, a clinical setting, and/or by user error, handling of theconversion reactor, and environmental factors, to name a few. Forexample, cracks can be formed in the structure which can provide achannel allowing flow of NO₂ through the reactor without conversion toNO, which in turn may be delivered to the patient. Further, cracks inthe structure may not be obvious until a gas flow is applied and/or NO₂breakthrough occurs. In another scenario, a crack in the porous solidstructure may not initially propagate all the way through the structureuntil sometime later under routine usage, when a toxic NO₂ suddenlyexits the reactor cartridge, which in turn may be delivered to thepatient. Accordingly, such compromised reactors may have unforeseenshortened lifetimes.

In addition, the use of multiple containers in a medical environmentholding toxic NO₂ presents the possibility of leaks that could releasethe NO₂ and subject both patients and staff to the toxic gas.

The above are only a few of the exemplary scenarios which can result ina patient receiving toxic NO₂ using the proposed techniques ofconverting toxic NO₂ to NO at the patient's bedside using an exhaustiblereactor cartridge when lifetime of reactor is unknown to the user. Giventhe risk of serious injury or death associated with inhalation of NO₂along with compounding factors and/or failure modes which may not bereadily ascertainable by a user (e.g., reactor exhaustion, channeling,compromised reactors, NO₂ breakthrough, leaks, etc.) a need exists toprovide both a reasonable assurance that the reactor cartridge isfunctional and a form of indication to inform a user of the amount oflifetime remaining for the reactor.

In addition, Nitrogen Dioxide, NO₂, reacts with water to give a mixtureof nitrous and nitric acids, as shown below.

2NO₂+H₂O→HNO₂HNO₃

The presence of excess water in a reactor cartridge can provide anenvironment where the NO₂ adsorbed on the consumable conversion mediacan react with the water before being converted to NO. Such reactionscan produce HNO₃ and HNO₂ within the reactor cartridge, which may becarried to a patient.

SUMMARY

There are several ways to address the above problems, includingmonitoring the use of the reactor(s), including indicators that visuallywarn a user of hazardous operating conditions, detectors that detect thepresence or absence of the chemical species of interest, and meters thatfollow the depletion and/or operation of the system in real time. Inaddition, various steps and processes may be implemented during themanufacturing and shipping of such reactor cartridges to help insure theproper performance and functioning of the cartridge when disseminatedinto the field, and safety features may be incorporated into the reactorcartridge to ensure that it has been properly handled and installed.

Principles and embodiment of the present invention relate to systems andmethods of preparing a NO₂-to-NO reactor cartridge and/or testing thesafety of the cartridge before being implemented for supplying NOthrough inhalation therapy to a patient.

Principles and embodiments of the present invention also relate tosystems and methods of assuring the safety and operability of reactorcartridges being manufactured.

Principles and embodiments of the present invention also relate to meansof monitoring the manufacture and assembly of an inhalation therapysystem that converts NO₂ to NO comprising a source of NO₂, a conversionreactor, and a delivery member.

Principles and embodiments of the present invention also relate tosystems and methods of reducing the likelihood or preventing asignificant and/or catastrophic breakthrough of NO₂ and preventingharmful or lethal doses of NO₂ from reaching the inhalation therapyrecipient due to channeling and/or breakage of the consumable conversionmedia in a reactor cartridge.

Principles and embodiments of the present invention also relate to asystem that produces a time-variable gas flow and tracks the flow andhumidity entering and/or leaving the reactor cartridge to inform a userof the amount of remaining life of a reactor and provides a safety checkfor proper reactor preparation and operation.

Principles and embodiments of the present invention also relate tosystems and methods to monitor and detect the physical treatment ofreactor cartridge(s) between initial assembly and final usage todetermine if a cartridge was physically abused.

Principles and embodiments of the present invention also relate to a NOgas delivery system for safely delivering a supply of NO to a recipient,comprising a gas source that supplies a gas, wherein the gas comprisesone or more of NO₂ or NO, a gas conduit connected to and in fluidcommunication with the gas source, a NO₂-to-NO reactor cartridgeconnected to and in fluid communication with the gas conduit, so as toallow gas to flow from the gas source to an inlet end of the conversionreactor, a ventilator, a delivery conduit connected to and in fluidcommunication with an outlet end of the reactor cartridge that allows NOgas from the conversion reactor to flow to a recipient, a computer inelectronic communication with the NO gas delivery system, which mayinclude the ventilator, over a communication path, wherein the computeris configured to receive electronic signals from the reactor cartridge,a flow meter, and/or ventilator and calculate a usage level forcomparison with a predetermined threshold value, and configured togenerate an actuating signal when the usage level falls below thethreshold value, a regulating means in electronic communication with thecomputer over a communication path, wherein the regulating means isconfigured to receive an actuating signal from the computer, and whereinthe regulating means halts the delivery of the gas to a recipient.

In addition, embodiments of the present invention relate to a reactorcartridge comprising an integrated NO₂ sensor for measuring the amountof NO₂ gas exiting the NO₂-to-NO reactor cartridge, a flow meter formeasuring the amount of NO₂ gas entering the reactor cartridge and/orgas being delivered to the recipient, an NO₂ sensor operationallyassociated with the delivery conduit to determine the presence of anunacceptable level of NO₂ in the gas being directed to the recipient, ora combination thereof.

Embodiments of the present invention also relate to systems and methodsof calibrating an integrated NO₂ sensor, and determining if anintegrated NO₂ sensor is out of calibration, wherein an alarm may begenerated and/or the reactor cartridge or delivery system may be placedinto a non-functional state.

Embodiments of the present invention also relate to a reactor cartridgecomprising an integrated pressure sensor for detecting the differentialpressure of gases entering and exiting the NO₂-to-NO reactor cartridge,and a meter to measure the differential pressure across the cartridge.

Embodiments of the present invention also relate to a reactor cartridgecomprising an integrated hygrometer (H₂O) sensor for detecting themoisture content of gases entering and/or exiting the NO₂-to-NO reactorcartridge, and a meter to measure the moisture level of the cartridge.

In addition, embodiments of the present invention relate to a reactorcartridge comprising an integrated accelerometer and/or orientationsensor for detecting the movement and/or angle of inclination of thecartridge, for example from a vertical position.

Principles and embodiments of the present invention relate generally toa system for safely delivering a supply of NO to a recipient, comprisinga gas source that supplies a gas, wherein the gas comprises one or moreof NO₂ or NO; a gas conduit connected to and in fluid communication withthe gas source; a NO₂-to-NO reactor cartridge connected to and in fluidcommunication with the gas conduit, so as to allow gas to flow from thegas source to an inlet end of the reactor cartridge; a flow meterconnected to and in fluid communication with the inlet end of thereactor cartridge and gas conduit to monitor the amount of gas deliveredto the reactor cartridge; a delivery conduit connected to and in fluidcommunication with an outlet end of the conversion reactor that allowsNO gas from the conversion reactor to flow to a recipient; a valveconnected to and in fluid communication with the delivery conduit toclose off the flow of gas to the recipient, and configured to receive anactuating signal from the computer; a computer in electroniccommunication with the flow meter over a communication path, and inelectronic communication with the valve, wherein the computer isconfigured to receive electronic signals from the flow meter andcalculate a usage value for comparison with a predetermined thresholdvalue, and configured to generate an actuating signal when the usagevalue reaches the threshold value, and communicate the actuating signalto the valve to close and stop the flow of gas to the recipient.

In addition, embodiments of the present invention relate to a systemwhich further comprises an outer housing encasing the gas source,wherein the outer housing is large enough to encapsulate the gas sourceand form an internal volume between the inside of the outer housing andthe gas source.

In addition, embodiments of the present invention relate to a systemwhich further comprises an absorbent material held within the internalvolume which is sufficient to react with all of the material potentiallyreleased from the gas source.

In addition, embodiments of the present invention relate to a systemwhich further comprises color agents intermixed with the absorbents, sothat a color change of the color agent occurs when the absorbentinteracts with the NO₂.

In addition, embodiments of the present invention relate to a systemwhich further comprises an NO₂ sensor operationally associated with thedelivery conduit to determine the presence of an unacceptable level ofNO₂ in the gas being directed to the recipient.

In addition, embodiments of the present invention relate to a systemwhich further comprises an impact sensor operationally associated withthe reactor cartridge to determine the level of shocks sustained by thereactor cartridge.

In addition, embodiments of the present invention relate to a systemwhich further comprises a memory chip operationally associated with thereactor cartridge to store reactor cartridge data on a non-transientcomputer readable medium, and wherein the memory chip is configured tobe in electronic communication with the computer.

Embodiments of the present invention relate to a system, wherein thecomputer is configured to be in electronic communication with the memorychip over a communication path, and can read the reactor cartridge datastored on a non-transient computer readable medium; and wherein thecomputer is configured to communicate the actuating signal to the valveto close and stop the flow of gas to the recipient if the reactorcartridge data indicates the reactor cartridge is inoperable.

In addition, embodiments of the present invention relate to a systemwhich further comprises a cartridge installation detector in electroniccommunication with the computer over a communication path thatidentifies when the reactor cartridge is properly coupled to the gasconduit and delivery conduit, and sends an actuating signal to thecomputer when the proper coupling of the reactor cartridge is detected;and wherein the computer prevents the gas delivery system from enteringan operational state until an actuating signal is received from thecartridge installation detector.

Embodiments of the present invention relate to a system, wherein thecomputer is configured to receive electronic signals from the flow meterand calculate a usage value, and store the calculated usage value on thenon-transient computer readable medium of the microchip for laterreference, and wherein the computer prevents the gas delivery systemfrom entering an operational state if the calculated usage data storedon the non-transient computer readable medium equals or exceeds thestored average expected lifetime of the reactor cartridge.

Principles and embodiments of the present invention relate generally toa reactor cartridge for converting NO₂ to NO, comprising an outerreactor shell; an inlet end wall that seals the inlet end of thereactor; an outlet end wall that seals the outlet end of the reactor toform an internal volume within the reactor cartridge; an inlet thatfacilitates connection of the reactor cartridge to a first gas conduitand allows passage of gas through the inlet end wall to the internalvolume; an outlet that facilitates connection of the reactor cartridgeto a second gas conduit and allows passage of gas through the outlet endwall to exit the reactor cartridge; a consumable conversion mediaretained within the internal volume of the reactor cartridge thatfacilitates conversion of an incoming NO₂ gas delivered to the inlet toan outgoing NO gas exiting at the outlet; a back end retainer positionedtowards the outlet of the reactor cartridge to prevent consumableconversion media from exiting the internal volume of the reactorcartridge through the outlet; a front end retainer positioned towardsthe inlet of the reactor cartridge to prevent consumable conversionmedia from exiting the internal volume of the reactor cartridge throughthe inlet, wherein the consumable conversion media is retained betweenthe front end retainer and the back end retainer; and a force-applyingmember positioned between the inlet end wall and the front end retainerto apply a pressure to the consumable conversion media.

In addition, embodiments of the present invention relate to a reactorcartridge which further comprises a memory chip affixed to the outerreactor shell, wherein the memory chip stores data relating to theconversion cartridge that the chip is affixed to on a non-transientcomputer readable medium.

Embodiments of the present invention relate to a reactor cartridge,wherein the stored data includes identification data, testing data,and/or cartridge life data.

In addition, embodiments of the present invention relate to a reactorcartridge which further comprises an impact sensor affixed to and/oroperatively associated with the reactor cartridge, wherein the impactsensor is configured to determine the number of impacts and/or theseverity of the impact(s) experienced by the reactor cartridge.

In addition, embodiments of the present invention relate to a reactorcartridge which further comprises an inlet with a keyed or polarizedcartridge connector and/or an outlet with a keyed or polarized cartridgeconnector, wherein the keyed or polarized inlet and/or outlet connectorsinteract with a mechanical interlock to ensure the reactor cartridge isinstalled with the correct orientation in a gas delivery system.

Principles and embodiments of the present invention relate generally toa method of testing reactor cartridges to determine an expectedlifetime, comprising assembling a number of reactor cartridges,comprising; providing a plurality of conversion cartridge shells;placing a first retainer on a support within the shell to partition offa section of the internal space; introducing a volume of a consumableconversion media into at least a portion of the internal volume of theconversion cartridge; placing a second retainer within the shell, thatis held in position against the volume of consumable conversion media bya force-applying member; closing an inlet end of the conversioncartridge shell with an inlet end wall, wherein an end of theforce-applying member is in contact with the inlet end wall and anopposite end of the force-applying member is in contact with the secondretainer, so that a force is applied to the volume of a consumableconversion media; and closing an outlet end of the conversion cartridgeshell with an outlet end wall; randomly selecting a number of reactorcartridges from the plurality of assembled reactor cartridges, where thenumber of cartridges selected for testing is less than the number ofcartridges assembled; installing a randomly selected reactor cartridgeinto a NO gas delivery system; testing the installed reactor cartridgeby a process comprising flowing a gas containing a predeterminedconcentration of NO2 through the installed reactor cartridge; measuringthe amount of NO2-containing gas fed into the reactor cartridge with aflow meter; detecting the presence of NO2 at the outlet of the reactorcartridge; calculating the amount of NO2 converted to NO by the reactorcartridge up to the time NO2 was detected at the outlet of the of thereactor cartridge with a computer; and replacing the installed reactorcartridge with a subsequent randomly selected cartridge and repeatingthe testing process until all randomly selected reactor cartridges havebeen tested.

In addition, embodiments of the present invention relate to a method oftesting reactor cartridges which further comprises calculating theamount of consumable conversion media used up to convert the amount ofNO₂ converted to NO; averaging the calculated amount of consumableconversion media used up for each tested reactor cartridge; calculatingthe average amount of NO₂ that would be converted to NO for the untestedplurality of assembled conversion cartridges.

In addition, embodiments of the present invention relate to a method oftesting reactor cartridges which further comprises affixing a memorychip comprising a non-transient computer readable medium, and configuredto communicate with a computer, to each of the conversion cartridgeshells; and storing the average amount of NO2 that would be converted toNO on the non-transient computer readable medium.

In addition, embodiments of the present invention relate to a method oftesting reactor cartridges which further comprises measuring the amountof H₂O present in the consumable conversion media with a H₂O sensor, andcomparing the measured amount of H₂O against a predetermined acceptablerange for the reactor cartridge.

In addition, embodiments of the present invention relate to a method oftesting reactor cartridges which further comprises measuring thedifferential gas pressure across the consumable conversion media todetermine if there is a low pressure differential due to channeling or acrack in the conversion media.

Principles and embodiments of the present invention also relate to amethod of monitoring the performance of an NO₂-to-NO reactor cartridge,comprising, providing an NO₂-to-NO reactor cartridge comprising aconversion media, incorporating one or more sensor probe(s) into thereactor cartridge and/or delivery system, wherein the one or more sensorprobes are operatively associated with conversion media, providing acomputer in electronic communication with the meter, providing at leastone meter operatively associated with at least one sensor probe, and inelectrical communication with the computer, detecting physical and/orchemical characteristics of the conversion media with the sensorprobe(s), measuring the detected physical and/or chemicalcharacteristics with the operatively associated meter, communicating themeasured physical and/or chemical characteristics to the computer;monitoring the communicated characteristics with the computer; anddisplaying the measured characteristic(s) and/or activating and alarm.

BRIEF DESCRIPTION OF THE DRAWINGS

Further features of embodiment of the present invention, their natureand various advantages will become more apparent upon consideration ofthe following detailed description, taken in conjunction with theaccompanying drawings, which are also illustrative of the best modecontemplated by the applicants, and in which like reference charactersrefer to like parts throughout, where:

FIGS. 1A-1B illustrates exemplary inhalation therapy systems, inaccordance with exemplary embodiments of the present invention;

FIG. 2 illustrates an exemplary housing around a source of NO₂, inaccordance with exemplary embodiments of the present invention;

FIGS. 3A-3C illustrate an exemplary NO₂-NO conversion reactor, inaccordance with exemplary embodiments of the present invention;

FIGS. 4A-4C illustrate another exemplary NO₂-NO conversion reactor, inaccordance with exemplary embodiments of the present invention;

FIGS. 5A-5B illustrate exemplary NO₂-NO reactor cartridge, in accordancewith exemplary embodiments of the present invention;

FIG. 6 illustrates an exemplary NO₂-NO reactor cartridge with amonolithic consumable conversion media showing gas flow, in accordancewith exemplary embodiments of the present invention;

FIG. 7 illustrates an exemplary NO₂-NO reactor cartridge with amonolithic consumable conversion media, in accordance with exemplaryembodiments of the present invention; and

FIG. 8 illustrates an exemplary inhalation therapy system with computercontrolled gas delivery, in accordance with exemplary embodiments of thepresent invention.

DETAILED DESCRIPTION

The principles and embodiments of the present invention relate tomethods and systems for safely providing NO to a recipient forinhalation therapy. As described above, there are many potential safetyissues that may arise from using a reactor cartridge that converts NO₂to NO, including errors and manufacturing deviations in the preparationof the cartridge reactor and of consumable reactants. Accordingly,various embodiments of the present invention provide systems and methodsof manufacturing, storing, and installing a NO₂-to-NO reactor cartridgeto alleviate the potential cartridge failure.

In embodiments of the present invention, the chemical and physicalcharacteristics of the cartridge reactor and consumable reactants can bemeasured by suitable techniques including but not limited to volumetricand mass flow rates through the cartridge, spectroscopic analysis ofconsumable reactants, inert products, and/or gases, sampling andchromatography of gases, wet chemical analysis and/or quantitativedetection of consumable reactants and/or gases, electrochemical analysisby voltammetry and/or amperometry, and/or quantitative or qualitativedetection of consumable reactants by color change.

In embodiments, meters can detect and/or measure various characteristicsof the conversion reactor and/or gas streams, including but not limitedto the concentration of ascorbic acid, the concentration ofdehydroascorbic acid, the concentration of water (H₂O), theconcentration of NO₂, the concentration of NO, the concentration of O₂,the concentration of HNO₃, the pH of at least a portion of theconversion reactor or water vapor exiting the reactor, the redoxpotentials of chemical species in the conversion reactor, the mass flowrate of gases, the conductance at the surface of the silica gel, and thehumidity of incoming and outgoing gases.

Various metering devices, apparatus, and methods have been furtherdescribed in “SYSTEMS AND METHODS FOR INDICATING LIFETIME OF ANNO₂-to-NO REACTOR CARTRIDGE USED TO DELIVER NO FOR INHALATION THERAPY TOA PATIENT.”

Various embodiments of the present invention can be used, modified,and/or be affiliated with various systems for delivering apharmaceutical gas to a patient receiving inhalation therapy. Thesesystems can include, but are not limited to, ventilators, CPAP/BiPAP andAPAP systems, pulsed delivery systems, breathing circuits, nasalcannulas, breathing masks, and/or any other system for delivering apharmaceutical gas to a patient receiving inhalation therapy.

Generally speaking, to provide NO inhalation therapy to patient in needthereof, these systems can include, but are not limited to, a source ofgas that can provide NO as a final product, a source of air flow, asource of oxygen, a conduit that contains and/or communicates the gasand air flow to a NO₂-to-NO reactor cartridge, a delivery conduit thatcontains and communicates the NO gas and air mixture from the conversionreactor to a recipient interface.

Referring to FIGS. 1A-1B, exemplary NO delivery systems are illustrated.

As shown in FIG. 1A, the embodiment of a NO gas delivery system 1comprises a source of gas 10 connected to and in fluid communicationwith a ventilator 60 via a gas source conduit 40 that can contain anddirect the gas from the gas source 10 to the ventilator 60. Theventilator 60 may provide a regulated flow of gas through the deliverysystem 1 to the recipient 90, which may have different specified flowpatterns. An air supply 20, which may be an air pump, compressor, orcentralized air supply, for example wall air in a hospital, also may beconnected to and in fluid communication with the ventilator 60 via a gasconduit 25. An optional supply of oxygen 30 may also be connected to andin fluid communication with the ventilator via a gas conduit 35, wherethe oxygen supply may augment the concentration of oxygen delivered to arecipient 90. The air, NO₂, and/or O₂, may be mixed prior to enteringthe ventilator 60 or within the ventilator. The ventilator 60 may beconnected to and in fluid communication with the gas source conduit 42,which can contain and direct the gas from the ventilator 60 to a firstconversion reactor 100. The first conversion reactor 100 may beconnected to and in fluid communication with the gas source conduit 42at an inlet side, and connected to and in fluid communication with a gassource conduit 44 at an outlet side. A humidifier 45 may be connected toand in fluid communication with the gas source conduit 44 at an inletside, and connected to and in fluid communication with the gas sourceconduit 47 at an outlet side. The gas source conduit 47 may contain anddirect the gas from the humidifier 45 to a second conversion reactor101, which may be the same as or different from conversion reactor 100.A gas delivery conduit 50 may be connected to and in fluid communicationwith the second conversion reactor 101 to contain and direct the gasfrom the outlet of the second conversion reactor 101 to the recipient90. A ventilator conduit 52 may be connected to and in fluidcommunication with a ventilator 60, and interfaced with the gas deliveryconduit 50, and/or recipient 90, for example with a Y-tube.

In embodiments, the humidifier helps maintain an acceptable level ofmoisture in the air/NO gas supply entering the second conversion reactor101 to ensure a sufficient amount of H₂O for the reactor to functionproperly.

In embodiments, the second conversion reactor 101 converts any NO₂ thatfailed to be converted by conversion reactor 100 and/or that has formedin the conduits and humidifier through reaction of NO with O₂ or H₂Oback into NO before NO₂ in the gas stream reaches a recipient 90.

In embodiments, a computer system may be connected to and in electricalcommunication with a ventilator 60, as well as automatic valves andregulators (e.g., pressurized air, solenoid, and solenoid pneumaticvalves), and various meters and detectors (e.g., flow meters, NO₂detector, H₂O detector, etc.).

As shown in FIG. 1B, another non-limiting embodiment of a NO gasdelivery system 1 comprises a source of gas 10, which may be a NO₂ gassource, which can be connected to and in fluid communication with gassource conduit 40 that can contain and direct the gas from the gassource 10 to a conversion reactor 100. A humidifier 45 may be connectedto and in fluid communication with the gas source conduit 40, andinserted between the gas source 10 and conversion cartridge 100 to addmoisture (i.e., H₂O) to the gas entering the conversion cartridge 100.An air supply 20, which may be an air pump, compressor, or wall air, maybe connected to and in fluid communication with the gas source conduit40 to provide a flow of ambient air with the NO₂ source gas. An optionalsupply of oxygen 30 may also be connected to and in fluid communicationwith the source conduit 40, for example, to supplement the amount ofoxygen being fed through the conduit(s). The source conduit 40 can beconnected to and in fluid communication with the conversion reactor 100,which in turn can be connected to and in fluid communication with a gasdelivery conduit 50 that contains and directs the gas from theconversion reactor to a patient 90. In embodiments, an NO gas source(not shown) may be connected to and in fluid communication with thesource conduit 40, alone or in combination with the NO₂ gas source, as abackup.

Principles and embodiments of the present invention also relate toproviding protective elements operatively associated with a source ofNO₂, and/or a reactor cartridge, which may comprise components to absorbany NO₂ that may leak out of the NO₂ source and/or reactor cartridge,and color agents that indicate the presence of NO₂.

In various embodiments, as shown in FIG. 2, a source of NO₂ gas 10 maybe encased within an outer housing 15 that surrounds the containerholding the NO₂ source material (e.g., NO₂ gas, N₂O₄ liquid, and gas,liquid, or solid, which may react to produce NO₂, etc.). The NO₂ gascontainer 10 and/or outer housing 15 may be glass, quartz, silica,steel, stainless steel, anodized aluminum, chemically resistant alloys(Waspaloya, fluoro-polymers (e.g., Teflon®), and combinations thereof(e.g., glass or fluoro-polymer lined stainless steel or aluminum). Inembodiments of the present invention, the outer housing 15 can be largeenough to encapsulate the NO₂ source container 10 or a reactor cartridgeto reduce or prevent any NO₂ gas from reaching the atmosphere, and forman internal volume between the inside of the outer housing and the NO₂source container sufficiently large to hold enough absorbent 17 to reactwith all of the gas or liquid possibly released from the NO₂ sourcecontainer 10. The size of the housing and amount of absorbent would berelated to the size of the NO₂ source container and amount of NO₂potentially generated. Reaction between the NO₂ source gas or liquid andthe absorbent should be complete, such that none of the NO₂ remainsafter interacting with the absorbent. A surplus of absorbent may beincluded to provide a safety factor to ensure all of the NO₂ is absorbedand/or reacted. A valve and feed line 11 may be connected to and influid communication with the NO₂ gas container 10, and pass through theouter housing 15 in a manner that forms a gas-tight seal (e.g., welding,brazing, gaskets, epoxies, etc.).

In embodiments of the present invention, the NO₂ may be absorbed byabsorbents, including silica gel, alumina, soda lime, activatedcarbon/charcoal, and magnesium sulfate.

In embodiments of the present invention, the absorbents may be treatedand/or intermixed with the color agents, so that a color change of thecolor agent occurs when the absorbent interacts with the NO₂ or when atleast a portion of the absorbent is used up. In embodiments of theinvention, the presence of NO₂ may be indicated by a color agent, whichmay be for example sulfanilic acid (diazotizing agent) in combinationwith N(1-naphthyl)ethylene diamine dihydrochloride, metalloporphyrins,for example (5,10,15,20-tetrraphenylporphyrin)-zinc, ethyl violet, andmalachite green. In a non-limiting example, in the absence of NO₂sulfanilic acid (diazotizing agent) in combination withN(1-naphthyl)ethylene diamine dihydrochloride has white color but yieldslight purple color at about 3.7 ppm and medium purple at about 10 ppm ofNO₂. In a non-limiting example, metalloporphyrins may change from purpleto yellow. In embodiments, the color agent may also indicate changes inpH that occurs upon exposure to NO₂.

In embodiments, the outer housing may be transparent (e.g., glass,quartz, fused quartz, polycarbonate) or have an opening in thenon-transparent material body (e.g., steel) with a transparent window(e.g., glass, quartz, fused quartz, polycarbonate), so that a user mayobserve any color change by the color change agent.

In embodiments of the present invention, the NO₂-to-NO reactorcartridge, also referred to as a conversion reactor or conversioncartridge, can include an outer reactor shell or body, an inlet, anoutlet, and a consumable conversion media including solid packingmaterial coated with consumable reactant, for example an antioxidant andwater, where the solid packing material can be retained within theinternal volume of the reactor shell, and where the coated packingmaterial provides a consumable reactant surface. The solid packingmaterial and consumable reactant coating form a consumable conversionmedia. In one or more embodiments, the antioxidant is ascorbic acid,which can be applied to the packing material in an aqueous solution, andthe packing material may be silica gel. Other antioxidants includesuitable reducing agents for the conversion of NO₂ to NO, such as alphatocopherol and gamma tocopherol. Other packing material may includecalcium sulfate dehydrate, calcium fluorophosphate dihydrate, zirconium(IV) oxide, zircon, titanium dioxide, and aluminum silicate, or anysuitable material that can be coated with consumable reactant and/orthat can be hydrated.

In embodiments of the present invention, the agents for the conversionof NO₂ to NO also may be toluidine, benzidine, and benzidinederivatives, as presented in U.S. Pat. No. 3,106,458 issued on Oct. 8,1963, to Grosskopf et al., and incorporated herein by reference in itsentirety. The benzidine may be for exampleN,N,N,N′-tetraphenylbenzidine, N,N′-dimethyl-N,N′ diphenylbenzidine, orN,N′ diphenylbenzidine, which may be combined with a strong acid on acarrier, such as silica gel, as a reagent for NO₂. The toluidine,benzidine, and benzidine derivatives may be deposited onto the carrierand exposed to NO₂, and the toluidine, benzidine, and benzidinederivatives undergo a color change upon such exposure. In embodimentsthe reaction between NO₂ and the aromatic amines produces NO and areactant product. For example, the N,N′ diphenylbenzidine can react withNO₂ to produce NO, H₂O, and NN-diphenyl-1,4-phenylenediamine.

Referring to FIGS. 3A-3C, a general example of a packed-type NO₂-to-NOreactor cartridge 100 is illustrated. The conversion reactor, as shownin FIG. 3A has a body with an outer annular wall 110, an inlet end wall120 that seals the inlet end of the reactor, an outlet end wall 130 thatseals the outlet end of the reactor to form an internal volume 150within the reactor 100. The reactor also has an inlet 140 thatfacilitates connection of the reactor 100 to a gas conduit (not shown)and allows passage of gas through the inlet end wall 120 to the internalvolume 150. An outlet 190 facilitates connection of the reactor 100 toanother gas conduit (not shown) and allows passage of gas through theoutlet end wall 130 to be delivered to a recipient. At least a portionof the internal volume 150 of the reactor 100 may contain a consumableconversion media 160 that facilitates conversion of an incoming NO₂ gasdelivered to the inlet 140 to an outgoing NO gas exiting at the outlet190.

In embodiments, the inlet and/or outlet may comprise a connector that iskeyed or polarized, so that the cartridge can only be installed with thecorrect orientation and gas flow direction. The conduits 40,42,47,50 mayalso comprise a mating connector that is keyed or polarized to match theparticular connector on the cartridge. In embodiments, cartridges100,101 may comprise connectors with different keying/polarizationfeatures, so that reactor cartridge 100 may not be interchanged orsubstituted with a reactor cartridge 101, and vise versa.

As shown in FIG. 3B, the embodiment of a NO₂-to-NO reactor cartridge 100comprises a consumable conversion media 160 comprising a flowable,granular or pelletized solid material that fills at least a portion ofthe internal volume formed by the annular wall 110 of the reactorcartridge 100. In embodiments, the consumable conversion media 160 maynot fill the entire volume of the reactor cartridge, so empty spaces maybe left towards the inlet side and/or outlet side of the cartridge.

As shown in FIG. 3C, the embodiment of a NO₂-to-NO reactor cartridge 100may comprise a front end retainer 155 positioned nearer the inlet 140and a back end retainer 165 opposite the front end retainer 155 andpositioned nearer to the outlet 190 of the reactor. In embodiments, afront end compression spring 157 may be positioned between the front endwall 120 and the front end retainer 155 to apply a pressure against theotherwise flowable packing material to compact it. In embodiments, aback end compression spring 167 may be positioned between the back endwall 130 and the back end retainer 165 to apply a pressure against theotherwise flowable packing material to compact it. The retainers 155,165and optionally one or more compression springs 157,167 hold theconsumable conversion media in place against shocks, vibration andhandling, so it does not shift and/or form channels. The retainersshould be sufficiently porous to permit gas to flow through withoutsignificant pressure drop relative to the pressure drop caused by theconsumable conversion media and/or the gas pressure provided by variousembodiments of the system 1.

Although reference for the embodiment has been made to compressionsprings, this is for convenience, and other mechanisms may be employedto apply a pressure to the retainer(s), including but not limited towave washers, compression washers, an elastomeric sleeve, foam, or oneor more of O-rings, which would take up a similar limited space and alsobe compatible with the operating environment, which may be referred toas force-applying member(s) and are considered within the scope of thepresent invention.

Although reference has been made to an annular or cylindrical wall,other shapes including but not limited to oval, elliptical,quadrilateral, and polygonal, are also contemplated and intended to fallwithin the scope of the invention. The general shape of the reactorcartridge, internal volume, and monolithic conversion media may bealtered without deviating from the scope of the present invention.

Referring to FIGS. 4A-4C, a general example of porous solid-typeNO₂-to-NO reactor cartridge 100 is illustrated. The conversion reactor100, as shown in FIG. 4A, may also comprise an outer annular wall 110,inlet end wall 120, outlet end wall 130, inlet 140 and outlet 190, andmay have a similar configuration and dimensions as a cartridge with apacked solid conversion media 160. However, differing from the abovedescribed packed-type NO₂-to-NO reactor cartridge, the consumableconversion media for the porous solid-type NO₂-to-NO reactor cartridge100 can be a coated porous, bonded or sintered structure, for example aglass frit or sintered silica gel, in the form of a porous, cylindricalwall 170 to provide a surface area for coating with the consumablereactant, for example ascorbic acid and water. An example of a sinteredsilica gel is described in U.S. Pat. No. 3,397,153 A issued Aug. 13,1968, to Sippel et al., and incorporated herein by reference in itsentirety.

Referring to FIGS. 4B-4C, a first end of the cylindrical wall 170 may becapped with an end wall 172 of similar porous material or closed offwith a non-porous disk. The second end of the cylindrical wall oppositethe first end may be affixed to the outlet end wall 130, such that thecylindrical wall 170 surrounds the outlet 190. Gas entering theconversion reactor 100 through the inlet 140 enters the internal volume150 of the reactor body including the gap 175 between the outer annularwall 110 and the porous cylindrical wall 170, and is forced through theporous cylindrical wall 170 under pressure, as may be produced by asystem 1. The porous cylinder wall 170 is affixed to the outlet end wall130 in a manner that prevents gas from penetrating between thecylindrical wall and end wall, as would be known in the art of bondingtechnology, so all of the gas exiting the cylinder should pass throughthe porous cylindrical wall 170. A porous cylindrical wall coated withconsumable reactants forms a monolithic consumable conversion media incontrast to a packed consumable conversion media, wherein monolithicrefers to a structure having a defined shape and determinable dimensionsin contrast to a packed material formed by a large number of separateparticles that flow if not retained within a volume.

In various embodiments, the consumable conversion media, therefore, canbe a cylindrical wall or a packed bed coated with the consumablereactants. The reactant gas (e.g., NO₂), may become absorbed onto thecoated surface (e.g., silica gel) and interact with the consumablereactants (e.g., ascorbic acid and water) to produce a product gas(e.g., NO), which desorbs from the surface of the consumable conversionmedia and is transported out of the conversion reactor by a carrier gas,which may be non-reactive (e.g., N₂), reactive (e.g., O₂, H₂O), or acombination thereof (e.g., air).

In various embodiments, the porous cylindrical wall 170 may comprise oneor more binders and/or reinforcements to increase the structuralstrength and integrity of the porous cylindrical wall 170 to stresses,strains, and impacts above the value the wall would have without suchadditional features. In various embodiments, the reinforcements may becarbon fibers, glass fibers, aramid fibers, mica, and high strengthceramics (e.g., silicon nitride, silicon-aluminum oxy nitride (sialon),silicon carbide, boron carbide, etc.), or a combination thereof, and thebinders, also referred to as a matrix, may be polyesters, epoxies,polyethylene, polypropylene, nylon, and vinyl esters, or a combinationthereof.

In various embodiments, the reinforcement and/or binder(s) may beincorporated into the silica to increase the composite's strength andresistance to impacts. In embodiments, the reinforcement and/orbinder(s) may be incorporated into the silica in an amount in the rangeof about 2 wt % to about 30 wt %, or alternatively in the range of 5 wt% to 20 wt %, or about 10 wt % to 15 wt %. In embodiments, the size ofthe cylindrical wall 170 may be increased to compensate for surface arealost to the reinforcements and binders.

It will be understood that the cross-sectional shape of NO₂-to-NOreactor cartridges, and elements thereof, can be any reasonablecross-sectional shape such as, but not limited to, round, ovoid,quadrilateral, and polygonal, to name a few. For ease, thecross-sectional shape of NO₂-to-NO reactor cartridges, and elementsthereof, is described as being round, or variations thereof. This ismerely for ease and is in no way meant to be a limitation.

FIGS. 5A-5B illustrate a cut-away view of a conversion reactor 100indicating the intended direction of gas flow through the internalvolume 150 and packed consumable conversion media 160.

FIG. 5A illustrates a conversion reactor with an impact sensor 200 and amemory chip 300 affixed to and operatively associated with the reactorcartridge, wherein the impact sensor and/or memory chip may beconfigured to be in electronic communication with a computer.

In the embodiment illustrated in FIG. 5B, the packing material may beheld within a portion of the internal volume by a front end retainer 155positioned nearer the inlet 140 and a back end retainer 165 opposite thefront end retainer 155 and positioned nearer to the outlet 190 of thereactor. There may be a gap between the inlet end wall 120 and the frontend retainer 155 that does not contain any packing material and forms anopen internal volume at the inlet 140. There may also be a gap betweenthe outlet end wall 130 and back end retainer 165 that does not containany packing material and forms an open internal volume at the outlet190. A general direction of gas flow through the cartridge is indicatedby arrows.

FIG. 6 illustrates a cut-away view of a conversion reactor 100indicating the intended direction of gas flow through the internalvolume 150 and cylindrical wall 170 of the monolithic consumableconversion media. The gas enters through the inlet 140 and passesthrough the internal volume 150 and gap 175 to the monolithic consumableconversion media, which can be semi-permeable. The gas passes throughthe porous cylindrical wall 170 of the semi-permeable, monolithic,consumable conversion media into the hollow space 180 and out throughthe outlet 190. NO₂ gas passing through a consumable reactant coatedcylindrical wall 170 can be converted into NO through interaction withconsumable reactants (e.g., ascorbic acid and H₂O) on the surfaces. Inexemplary embodiments, the thickness of the cylindrical wall should begreater than the mean free path of the gas through the porous wallmaterial to ensure all of the NO₂ interacts with a consumable reactantcoated surface before reaching the hollow space 180.

While the direction of gas flow has been illustrated as from theexterior of the semi-permeable wall 170 into the interior hollow space180, in embodiments the direction may be reversed or in other directionswithout departing from the spirit and scope of the invention.

Principles and embodiments of the present invention relate to systemsand methods of manufacturing a conversion cartridge comprising aconsumable conversion media, an external shell of the conversioncartridge may be provided, where the external shell comprises a wallhaving a shape and an open internal space that can accommodate apredetermined weight or volume of conversion media. In embodiments afirst retainer may be placed within the shell to partition off a sectionof the internal space to hold a packed material.

In various embodiments, a first retainer comprising a gas-permeable diskmay be placed within the conversion cartridge shell, and may be held inposition by a support, for example a shoulder, a plurality ofprotrusions, or a standoff. The retainer may have a shape that conformsto the internal shape of the shell. In embodiments, the retainer may beconfigured and dimensioned to fit snugly within the shell so that a gapbetween the retainer edge and cartridge wall is less than the dimensionsof the packed material forming the conversion media. For example, if theconversion media is comprised of silica gel having a particle diameterof 100 microns, the clearance space between the retainer edge and theinside of the cartridge wall should be less than 100 microns to preventthe silica particles from circumventing the retainer. In embodiments, aflexible washer, gasket, or O-ring may be operatively associated withthe retainer to fill or block the clearance space between the retaineredge and the inside of the cartridge wall.

In various embodiments, a force-applying member (e.g., compressionspring) may be placed between a shoulder, protrusions, or a standoff,and the retained to apply a pressure to the retainer and compensate fordecreases in volume of the packed conversion media.

In various embodiments, the consumable conversion media comprises asolid packing material, for example silica gel having a particle size ofabout 30 to about 1000 microns, or about 60 to 500 microns. The packingmaterial may be in the form of a granular or pelletized flowable solid.

In embodiments, the solid packing material may be coated with consumablereactant, for example an antioxidant and water, where the packingmaterial provides a surface for the consumable reactants.

Ascorbic acid has a solubility in water of 330 g/l. In embodimentsutilizing ascorbic acid, up to 330 g/l may be dissolved in water toproduce a solution for coating the solid packing material. In someembodiments, a saturated solution of ascorbic acid in water is used toprepare the consumable conversion media with the antioxidant and water.

Alpha—tocopherols are essentially insoluble in water, so would beapplied neat or using a suitable organic solvent, for example acetone,to coat the solid packing material.

In various embodiments, a predetermined weight of antioxidant may bedissolved in a suitable carrier may be brought into contact with apredetermined weight or volume of solid packing material, and thesolvent allowed to evaporate, so the predetermined weight of antioxidantis deposited onto the surface of the packing material.

In various embodiments, a predetermined weight of antioxidant may bedissolved in a predetermined amount of solvent to provide a solution ofpredetermined concentration. An amount of the solution may be passedthrough a predetermined weight or volume of solid packing material, andexcess solution drained from the packing material, which may then bedried, so a predetermined weight of antioxidant is deposited onto thesurface of the packing material.

In embodiments, the coated packing material provides a flowable form ofconsumable conversion media, which may be introduced into at least aportion of the internal volume of the conversion cartridge. A specificweight or volume of consumable conversion media may be poured into aconversion cartridge, which already has a first retainer suitablypositioned in the cartridge to prevent passage of the conversion mediaout of the internal volume or even the cartridge outlet.

In various embodiments, a second retainer comprising a gas-permeabledisk may be placed within the conversion cartridge shell, and may beheld in position against a volume of consumable conversion media by aforce-applying member (e.g., compression spring), which places a forceon the second retainer to assist in compacting and maintaining theconsumable conversion media within the predetermined internal volume.The retainer may have a shape that conforms to the internal shape of theshell. In embodiments, the retainer may be configured and dimensioned tofit snugly within the shell so that a gap between the retainer edge andcartridge wall is less than the dimensions of the packed materialforming the conversion media.

In various embodiments, the shell of the conversion cartridge may beclosed at each end with an end wall, such that the intended outlet sideof the cartridge is sealed by an outlet end wall and the opposite orinlet side of the cartridge is sealed by an inlet end wall. The inletand wall and outlet end wall may have inlet and outlet openings to allowgas(es) to enter and exit the reactor cartridge.

In various embodiments, the one or more force-applying member(s) may beheld in position and be compressed against the respective end wall toprovide suitable pressure against the particles of the consumableconversion media, so the media is held in place over an extended periodof time.

In various embodiments relating to a method of manufacturing asemi-permeable, monolithic, consumable conversion media and conversioncartridge, a predetermined weight of antioxidant may be dissolved in asuitable carrier and coated onto a porous cylindrical wall of sinteredor bonded packing material to form a monolith conversion media. Themonolith conversion media may be bonded to the outlet end wall 130 toform a gas-tight seal, and the outlet end wall sealed to the annularcartridge wall 110 to form a gas-tight seal. An inlet end wall may besealed to the annular cartridge wall 110 to form a gas-tight seal.

It will be understood that principles and embodiments described withreference to porous solid-type NO₂-to-NO reactor cartridges, andelements thereof, and principles and embodiments described withreference to packed-type NO₂-to-NO reactor cartridge, and elementsthereof, can, when applicable, be implemented in either configuration.This is merely for ease and is in no way meant to be a limitation.Accordingly, reference made to one type of reactor cartridge or another,at times, is made for ease and is not meant to be limited to that typeof reactor cartridge.

When the reactor is configured as a packed column, incoming NO₂interacts with the consumable reactant's active consumable conversionmedia closest to the reactor inlet first. As the conversion material isused up by exposure to the NO₂, additional incoming NO₂ passes furtherinto the packed column before reaching an active surface of theconsumable reactant. This process proceeds through the packed materialuntil NO₂ can pass all the way through the reactor without interactingwith a consumable reactant surface. At this point NO₂ breakthroughoccurs, and the reactor is effectively depleted.

Breakthrough may be when NO₂ is at a concentration of about 0.1 ppm. 0.2ppm, 0.3 ppm, 0.4 ppm, 0.5 ppm, 0.6 ppm, 0.7 ppm, 0.8 ppm, 0.9 ppm, 1ppm, 1.5 ppm, 2 ppm, 2.5 ppm, 3 ppm, 3.5 ppm, 4 ppm, 4.5 ppm, 5 ppm, 6ppm, 7 ppm, 8 ppm, 9 ppm or 10 ppm in the gas stream exiting theNO₂-to-NO reactor cartridge.

Principles and embodiments of the present invention also relate to asafety interlock system that may automatically identify a specificconversion cartridge when it is installed in a NO gas delivery system.

In embodiments, a memory chip may be affixed to a conversion cartridge,where the memory chip stores data relating to the specific conversioncartridge. In various embodiments, the stored data may includeidentification data, testing data, and/or cartridge life data.

In various embodiments, identification data may include for example acartridge serial number, a lot and/or batch number, a production date,an expiration date, or a combination of such identification data. Thisidentification data may be used to ensure usage of desired cartridges.For example, using this data, if cartridges (e.g., cartridge 100,cartridge 101) are from the same lot, batch, production date, expirationdate, manufacturing facility, etc. are used an alarm may go offindicating to the user that they cannot use the cartridge and/or use ofthe cartridges may not be allowed.

In various embodiments, testing data may include for example a weight ofconsumable conversion media within the conversion cartridge, values oftest results showing conversion efficiency of NO₂ to NO, pressure dropacross the consumable conversion media, humidity level of the consumableconversion media, a pass or no-pass test rating for the cartridge, or acombination of such test data.

In various embodiments, cartridge life data may include for exampleaverage expected cartridge life calculated from test data, totalexpected NO₂ conversion by weight, concentration, and/or volume,expected duration of usage at an average gas flow rate, or a combinationof such cartridge life data.

In various embodiments, the memory chip may comprise a non-transientcomputer-readable media, and a connector operatively associated with thenon-transient computer-readable media over one or more electrical lines,where a computer controlling the NO gas delivery system is configuredand adapted to connect to and electrically interact with thenon-transient computer-readable media to read the stored data.

In various embodiments, the NO gas delivery system will not enter anoperational state unless the computer controlling the NO gas deliverysystem can identify the installed conversion cartridge from theidentification data stored in the non-transient computer-readable mediumof the memory chip, and receives confirmation that the specificconversion cartridge has acceptable test values and/or a pass rating. Inembodiments, the communication of data from the memory chip to thecomputer controller acts as at least a portion of a NO gas deliverysystem interlock. A conversion cartridge with an associated memory chipstoring data that indicates for example that the cartridge has passed anexpiration date, has marginal test results, or indicates that theconsumable conversion media has previously been used up, may register asthe reactor cartridge being inoperable.

In various embodiments, a cartridge installation detector may determinewhether the conversion cartridge is properly coupled to the gas sourceconduit and the conversion cartridge is properly coupled to the deliveryconduit. In embodiments, the cartridge installation detector may be aproximity switch, a leaf switch, or a closed-circuit detector thatidentifies a closed circuit when the cartridge is coupled to theconduit(s). In embodiments, the detection of the proper mechanicalinstallation of the conversion cartridge acts as at least a portion of aNO gas delivery system interlock.

Without such an interlock, an NO₂ source may be activated with an openended conduit and no reactor cartridge to convert the toxic NO₂ gas intoNO before it is released.

In various embodiments, the keyed or polarized cartridge connectorsinteract with the mechanical interlock to ensure the cartridge isinstalled with the correct orientation in the gas delivery system.

In various embodiments, this interlock system effectively shuts down theNO gas delivery system until an identifiable and viable conversioncartridge is properly installed both mechanically and electronically inthe gas delivery system.

In various embodiments, the NO gas delivery system may transmit usagedata from the computer controller to the memory chip for storage in thenon-transient computer readable medium. The usage data may include forexample the weight, volume, and/or concentration of NO₂ that has beenfed into the conversion cartridge while it was installed in the NO gasdelivery system. The stored usage data may be read by a delivery systemcomputer controller to determine the anticipated remaining life of thespecific installed conversion cartridge based on the previous weight,concentration, and/or volume flow of NO₂ through the cartridge.

In various embodiments, the NO gas delivery system may not enter anoperational state unless the computer controlling the NO gas deliverysystem can determine that the installed cartridge has a suitableremaining life time for the expected dosage and/or treatment time.

In various embodiments, the identification data, testing data, and/orcartridge life data may be printed as a 1-D or 2-D bar code label thatmay be physically affixed to a conversion cartridge, for example with anadhesive, and the NO gas delivery system will not enter an operationalstate unless the computer controlling the NO gas delivery system canread and identify the encoded cartridge from the affixed bar code, forexample by scanning the bar code with a bar code reader in communicationwith the computer.

In various embodiments, a communication path may be a physical line(e.g., cooper wire, fiber optics) connected to two or more electronicdevices that can carry an electronic signal, or a wireless communicationpath, for example radio communication, infrared communication, ormicrowave communication, that can convey an electronic signal betweentwo or more electronic devices without a physical line connection.

Once a conversion cartridge has been manufactured, it may be tested todetermine that it is operating properly. For example, it may be checkedfor the correct moisture content, the proper pressure drop between theinlet and outlet end, and NO₂ may be introduce to determine that theconsumable media is suitably active, so that no NO₂ exits the cartridge.

In various embodiments, the moisture content of the conversion media ina sealed conversion cartridge may be tested with a moisture sensorwithin the cartridge and external leads or connectors that can be placedin communication with an appropriate meter was would be known in theart.

In various embodiments, a moisture sensor may be placed within a conduitconnected to and in fluid communication with the outlet of a sealedconversion cartridge to determine the moisture content of the gasexiting the cartridge, and correlating the amount of evaporated moistureexiting the cartridge with the amount of moisture present in theconsumable conversion media. The relationship between gas moisture andmedia moisture may have been previously determined through testing andstatistical calculations.

With an understanding of the delivery systems and NO₂-to-NO reactorcartridges, principles and embodiments of the present invention relatingto systems and methods of determining the remaining useful life of aNO₂-to-NO reactor cartridge and/or a breakthrough of NO₂, and providingan indication of the remaining useful life and/or breakthrough can nowbe presented in context and in greater detail. It will be understoodthat various embodiments can be used, modified, and/or be affiliatedwith systems for NO inhalation therapy that can include an initialsource of gas that is NO and/or NO₂.

In exemplary embodiments, the remaining useful life of NO₂-to-NO reactorcartridge can be determined and/or provided to users by one or moremeters, such as dosage meters and/or flow meters. In exemplaryembodiments, meters can be integral with and/or operatively associatedwith a NO₂-to-NO reactor cartridge, and/or integrated with the gasdelivery system.

In exemplary embodiments, meters can include and/or be operativelyassociated with one or more sensors, which in turn may be operativelyassociated with at least a portion of the conversion reactor. Sensor canbe, but is not limited to, a flow sensor, a spectrophotometric sensor, achemical sensor, an electrochemical sensor, a pH sensor, a moisturesensor, or a combination of one or more sensors.

Principles and embodiments of the present invention also relate todetermining the activity of the consumable conversion media, theconcentration of various components in the gas stream at variouslocations in the system, or both. Consumable conversion media componentsof interest can include ascorbic acid, dehydroascorbic acid, nitricacid, water, or combinations thereof. Gasses of interest can includeNO₂, NO, and O₂, or combinations thereof.

In various embodiments, the useful lifetime of a reactor cartridge maybe determined by a number of factors including but not limited to theoverall surface area of the loose or monolithic packing material, theweight of antioxidant retained on the packing material surface, theamount of H₂O available to react with the antioxidant and NO₂, thedurability of the reactor cartridge and packing material.

Principles and embodiments of the present invention relate to methods ofdetermining the average expected lifetime of a cartridge.

The average expected lifetime of a cartridge may be determined byexperimental measurements, stoichiometric calculations, or a combinationthereof.

For example, the average expected lifetime may be based on the amount ofconsumable conversion media available to react with incoming NO₂ gas.This may be calculated from the molar mass of antioxidant applied to thepacking material by differential weighing before and after applicationof the antioxidant. In addition, the reactor cartridge may be testedwith a flow of NO₂ gas of known concentration, since actual values maydiffer from the calculated values due to some of the reactants beinginaccessible to the gas after packing or final assembly of a reactorcartridge.

In an embodiments, a method may comprise preparing a plurality ofstandard weights of consumable conversion media, calculating thestoichiometric amount of reactants present in the consumable conversionmedia for the measured weight, passing a NO₂ gas through the consumableconversion media until a predetermined concentration of NO₂ exits thecartridge indicating that breakthrough has occurred and the consumableconversion media has been exhausted. A ratio of the measured amount ofNO₂ conversion determined by testing to the calculated amount of NO₂conversion can be determined, and the ratio correlated with the initialdifferential weight measured for cartridges that are not tested toexhaustion to determine an expected amount of NO₂ that can be convertedby the cartridge. However, such untested cartridges may be tested withNO₂ or N₂ gas(es) for other determinations.

In embodiments, the average amount of consumable conversion mediaavailable to react with incoming NO₂ gas for each reactor cartridge maybe determined, and stored in the memory chip of the cartridges for theparticular production lot.

Principles and embodiments of the present invention relate to a methodof testing for NO conversion efficiency across the entire working flowrange of a delivery system, for example the flow patterns of aventilator, or maximum regulated flow intended from a compressed gascylinder. In various embodiments, a cartridge to be tested may beinstalled in a gas delivery system, and exposed to various operatingparameters.

In an embodiment, NO₂ may be injected into a reactor cartridge at aspecified concentration and flow rate, and the concentrations of NO₂ andNO detected at the outlet of the cartridge, where the total amount ofNO₂ injected into the cartridge is less than 0.1% of the expected amountof NO₂ that can be converted by the cartridge, so as not to measurablyreduce the expected lifetime. The injected concentration and flow ratemay be varied during the test to match flow patterns of a ventilator, sodifferent flow waveforms simulate different types of ventilation and theconversion is tested across the entire working flow range of a deliverysystem. This testing can confirm that a cartridge is capable of fullconversion (e.g., 99.9%) even at a maximum flow rate withoutbreakthrough.

In embodiments the values of NO₂ and NO detected at the outlet of thecartridge and/or a pass rating for conversion may be stored in thetested conversion cartridge.

In embodiments, the test system may comprise a computer and interlockarrangement as described herein, such that testing may not be conductedunless the cartridge is properly installed and the memory chip is inelectronic communication with the computer, and capable of storing thetest values.

Principles and embodiments of the present invention relate to a methodof testing for channeling and structural integrity of the consumableconversion media by introducing N₂ at a predetermined pressure into thecartridge inlet and measuring the differential pressure drop across theconversion media. A pressure drop greater than a threshold value wouldindicate that a path of lower resistance is present in the reactorcartridge being tested, for example a channel and/or crack depending onthe form of consumable conversion media, and the cartridge is thereforeunsafe and/or inoperable.

In embodiments the values of NO₂ and NO detected at the outlet of thecartridge and/or a pass rating for conversion may be stored in thetested conversion cartridge.

In exemplary embodiments, a statistical number or percentage ofunreacted gas molecules (e.g., NO₂) that would traverse the distancewithout conversion to a product molecule (e.g., NO), where the numbermay be set at an absolute concentration such as 0.1 ppm NO₂, or apercentage may be set at a relative amount such as 1% of NO₂ enteringthe reactor. Additional sensor locations may be positioned at othersample points of interest, such as along the periphery of the packedmaterial to detect channeling, buried to different depths within theconsumable conversion media to detect conversion fronts, and/or at thegas inlet or gas outlet to detect gas concentration(s) before or afterinteraction with the consumable conversion media.

Once a cartridge has been manufactured, sealed, and tested, it may bepackaged for storage, delivery, and to provide a safe and protectedenvironment before being used.

In embodiments, the packaging may provide a closed environment thatprevents or reduces the shock and impacts suffered by a cartridge, whilemaintaining the internal moisture content. The packaging may beair-tight around the cartridge to reduce the likelihood of gases ormoisture entering or escaping the cartridge during storage and/orshipment.

In embodiments, the packaging may comprise a supply of H2O, so thecartridge remains fully hydrated over prolonged periods of storage andshipping.

In embodiments, the packaging may comprise an impact sensor that couldindicate whether the structural integrity of the packaged conversioncartridge may have been compromised between manufacturing and unpackingby an end user. The impact sensor may be one of the sensors describedherein to be directly affixed to a cartridge, and may be in addition toan impact sensor also affixed to the packaged conversion cartridge.

Principles and embodiments of the present invention relate to systemsand methods for determining if a reactor cartridge has been subjected toinappropriate handling and/or shocks that could be transmitted throughthe reactor cartridge housing and affect the conversion media, as mightoccur in a manufacturing-warehousing setting and/or during transport andstorage by a customer due to rough handling of the conversion reactor bythe various actors.

In embodiments of the present invention, shocks may be detected byimpact sensors comprising a visually observable tube that may be affixedto and/or operatively associated with a reactor cartridge at some pointduring the manufacturing process, for example before or after loading ofthe conversion media into the cartridge body. Such a tube may changecolors when it experiences a force of predetermined magnitude, therebyindicating questionable physical integrity of the cartridge prior toactual use.

An impact sensor may be calibrated to provide a physical indication thatthe cartridge body, and thereby any conversion media within thecartridge body, has experienced a shock of sufficient force and/orduration to compromise the physical integrity of the reactor cartridgeand/or conversion media. For example, the porous cylindrical wall coatedwith consumable reactants of a monolithic consumable conversion mediamay become cracked if subjected to a sufficient force, as determined byexperiments (e.g., drop tests). Similarly, the particulate matter of apacked consumable conversion media for example may fracture and therebysuffer a reduction in volume, as well as settle sufficiently to permitchanneling. For example, silica granules may have a crush strength ofbetween about 5 and 30 pounds.

In various embodiments, an impact sensor may be a solid state detector,an electromechanical detector, an electrical or electronic detector, amicro-electro-mechanical system (MEMS) detector, or a mechanicaldetector. The impact detectors may be accelerometers. Anelectromechanical detector may be, for example, a reed switch that isactivated by the movement of a ring magnet, as known in the art. A solidstate detector may be a Hall Effect sensor operatively associated with amagnet, as would be known in the art. An electrical or electronicdetector may be for example a piezoelectric, piezoresistive orcapacitive detector, as would be known in the art. A MEMS detector maybe for example a cantilevered beam device, as would be known in the art.

In various embodiments, the impact sensor may be a detector in a singleplane or two or more detectors operating in a plurality of perpendicularplanes.

In various embodiments, the one or more impact sensor(s) may be incommunication and operatively associated with suitable analog and/ordigital electronics, for example a meter, that is configured to receiveand measure the analog or digital electrical signal(s) produced by theimpact sensor(s).

In various embodiments, the impact sensor may be configured to determinethe number of impacts and/or the severity of the impact(s) experiencedby the associated reactor cartridge. The values generated by the impactsensor may be stored in a non-transient memory, for example flashmemory, for later retrieval and/or analysis to determine if anyparticular impact was sever enough to possibly compromise the integrityand/or proper functioning of a conversion cartridge, or if multipleimpact events may have caused a total amount of force sufficient todamage or compromise the integrity and/or proper functioning of aconversion cartridge.

In various embodiments, the impact sensor may be affixed and/oroperatively associated with a conversion cartridge to detect if and/orwhen the conversion cartridge experiences an impact, for example frombeing dropped during manufacturing, packaging shipment, stocking,installation, usage, or any other handling. In various embodiments, animpact sensor may be affixed and/or operatively associated with thepackaging container within which a conversion cartridge may be placedafter manufacturing for protection during shipping and storage.

FIG. 7 illustrates an exemplary NO₂-NO reactor cartridge with amonolithic consumable conversion media, an impact sensor 200 affixed tothe wall on the outside of the reactor cartridge, and a memory chip 300affixed to the wall on the outside of the reactor cartridge, wherein theimpact sensor and/or memory chip are operatively associated with thecartridge, and may be configured to be in electronic communication witha computer.

An impact sensor and/or meter may be configured to detect and/or measurethe various overall accelerations and/or forces a cartridge or packagingmay experience even if a sudden impact, for example from falling andhitting the ground or an object, does not occur. For example, suddenstops, starts, and turns by a truck or forklift conveying a conversioncartridge from one location to another location may generate forces onthe conversion cartridge that should be monitored even though thecartridge and/or packaging appears undamaged when received by anend-user.

In various embodiments, the impact sensor may be an inertial measurementunit with multiple degrees of freedom.

In embodiments of the present invention, the determination thatbreakthrough of the NO₂ is imminent can be used to actuate a regulatingdevice to halt the delivery of at least the NO₂ gas to the recipientbefore poisoning occurs. The regulating device may cut off flow of NO₂from its source, cut off gas flow exiting the conversion reactor, divertair flow around the conversion reactor to continue air/O₂ delivery to arecipient without NO, or divert flow of the NO₂/air mixture to anauxiliary conversion reactor depending upon the system configuration andtherapy protocols for the recipient.

In embodiments a sample of gas exiting the conversion reactor may bediverted from the delivery conduit into a side stream. The side streamof gases may be passed through the transparent tubular sectioncontaining the material that changes color, introduced into aspectrophotometer, a mass spectrometer (e.g. for determining theconcentration of gases, etc.), or reaction vessels that produce a knownchemical response to the gases of interest.

In an embodiment, one or more fiber optic probe(s) may be insertedthrough the annular wall of the conversion reactor, such that the probecan detect changes in the ascorbic acid, dehydroascorbic acid, nitricacid, or combinations thereof, at a location along the length of thepacked reactor. A measurement of the ascorbic acid, dehydroascorbicacid, nitric acid, or combinations thereof would be indicative of theamount of consumable reactant activity remaining for the reactor, basedupon the mean-free path of gaseous NO₂, whereby a predetermined changein ascorbic acid, dehydroascorbic acid, nitric acid, or combinationsthereof indicates that the reactor has a limited conversion capacityremaining. The value of the predetermined change can be correlated withthe extent of reactor life remaining or the amount of consumableconversion media used up through suitable calibration and statisticalanalysis.

The combination of a fiber optic sensor probe and a spectrometer a meansfor monitoring the functioning of the conversion reactor and determininga lifetime of the conversion media.

Principles and embodiments of the present invention relate to detectingand/or measure the presence of nitric and/or nitrous acid, and pH todetermine if unconverted NO2 is reacting to form acidic by-products.

The combination of an electrochemical sensor probe and voltmeter and/orammeter provides a means for monitoring the functioning of theconversion reactor and determining a lifetime of the conversion media.

In an embodiment, the sensor probes can be micro pH sensors that candetect changes in pH due to the conversion of ascorbic acid todehydroascorbic acid. Micro pH sensors can have a 1 mm or sub-1 mmdetection tip that can be inserted through a suitable opening in theannular wall of the conversion reactor configured and dimensioned toreceive the pH sensor. The sensor can be electrically connected to anelectric circuit (e.g., pH meter) that detects changes in pH, as isknown in the art, and may communicate an electric signal to a computerfor display and/or triggering an alarm.

The combination of a pH sensor probe and pH meter provides a means formonitoring the functioning of the conversion reactor and determining alifetime of the conversion media.

In an embodiment, the sensor probes may be micro-conductivity sensorsthat can detect changes in the conductivity of the media surface due toreduced amount of water on the surface and/or differences inconductivity between the ascorbic acid and dehydroascorbic acid on thesurface.

The combination of a conductivity sensor probe and voltmeter and/orammeter provides a means for monitoring the functioning of theconversion reactor and determining a lifetime of the conversion media.

In an embodiment, the sensor probes may be magnetic probes sensors thatcan detect changes in the conductivity of the media surface due toreduced amount of water on the surface and/or differences inconductivity between the ascorbic acid and dehydroascorbic acid on thesurface.

In an embodiment of the present invention, a meter may be placed at thedistal end of the conversion reactor outlet to detect one or more gassesof interest exiting the reactor, in particular, an NO₂ sensor probe maybe located in the delivery conduit connected to the outlet to measurethe amount of NO₂ leaving the conversion reactor. The sensor probe maybe a chemical or electrochemical sensor that reacts with the exiting NO₂and converts it to another chemical species, thereby removing thedetected amount of NO₂ from the delivery gas stream flowing to arecipient.

Principles and embodiments of the present invention relate todetermining the mass and/or volumetric amount of NO₂ that can beconverted to NO by a conversion reactor, applying a safety margin to thedetermined volume of NO₂, and recording the determined value for laterreference in a memory chip affixed to the conversion cartridge.

In an embodiment, the safety factor is applied to compensate forstatistical variations in manufacturing, tolerances, and performancecharacteristics of the reactor, as well as real-world inaccuracies inmeasurements. The determined value and safety factor establishes atheoretical NO₂ breakthrough value at which the reactor would beconsidered depleted and requiring replacement to maintain safeoperation.

In embodiments, the amount of NO₂ passing into a characterized reactorcartridge can be measured by an appropriate mass flow meter(s), forexample a vane flow meter, a hot wire flow meter, a membrane temperaturesensor, or a Karman Vortex meter. Once the cumulative amount of NO₂measured by the flow meter reaches the determined value of the reactor,flow of the NO₂ can be halted to prevent breakthrough to a recipient. Inembodiments, a flow meter can be placed between the gas source and theconversion reactor. A valve can be placed downstream of the flow meterand before the conversion reactor. When the amount of gas passingthrough the flow meter reaches the theoretical NO₂ breakthrough value, acomputer can trigger the valve downstream of the flow meter to close,thereby shutting off gas flow to the reactor and halting the delivery ofNO/NO₂ to a recipient. In embodiments, an auxiliary air/O₂ line can beprovided in parallel to the conversion reactor line, so that air/O₂ maycontinue to flow to the recipient after the NO₂ gas source is valvedoff.

FIG. 8 illustrates a gas delivery system 1 having a gas source 10 thatcan supply for example NO₂ through a source conduit 40 to a flow meter43. Gas exiting the flow meter can be fluidly communicated to a valve 47and from the valve 47 to a conversion reactor 100 by the source conduit40. Gas entering the conversion reactor 100 may be converted to aproduct gas, for example NO, and fluidly communicated from the reactorto a recipient through a delivery conduit 50. A computer 800 inelectrical communication with the flow meter 43 monitors the amount ofgas passing through the meter and can calculate the amount of NO₂ fed tothe conversion reactor based on its concentration in the gas source 10.When the computer 800 determines that the amount of NO₂ fed to theconversion reactor has reached a predetermined value established for thereactor cartridge's expected life, the computer can send an electricalsignal to the valve 47 triggering it to close in order to prevent toxicNO₂ from flowing through an exhausted conversion reactor 100 andreaching the recipient.

In an embodiment, an indication that the reactor cartridge is nowexhausted may be stored in the non-transient computer readable medium inthe memory chip affixed to the cartridge. This exhaustion indicator maybe used to prevent the cartridge from accidently being reinstalled in adelivery system once it is no longer functional. In embodiments, theexhaustion indicator may be read by the system computer, and prevent thesystem from entering an operation state. An audible and/or visualwarning that the cartridge is no longer any good may also be provided toa user.

In an embodiment, a valve 57 may be connected to and in fluidcommunication with the delivery conduit 50 and an air supply 20, and avalve 67 may be located between the air supply 20 and gas source 10.When the computer 800 determines that the amount of NO₂ fed to theconversion reactor has reached a predetermined value established for thereactors expected life, the computer 800 can send an electrical signalto valve 57 to open at the same time that valve 47 is triggered toclose, in order to continue providing air to the recipient through thedelivery conduit without any NO₂ or product gases. A valve 67 may betriggered to close by the computer 800 to isolate the air supply 20 fromthe source gas 10, so only air is provide through alternate conduit 60.

In another embodiment, a gas source 65 supplying NO may be connected toand in fluid communication with the air supply 20 and alternate conduit60 to provide a predetermined concentration of NO to the recipient whenvalve 47 closes.

In embodiments of the present invention, the determination by the systemcomputer that potential breakthrough of the NO₂ is imminent due to thecartridge converting the average expected amount of NO₂ can be used toactuate a regulating device to halt the delivery of at least the NO₂ gasto the recipient before poisoning occurs. The regulating device may cutoff flow of NO₂ from its source, cut off gas flow exiting the conversionreactor, divert air flow around the conversion reactor to continueair/O₂ delivery to a recipient without NO, or divert flow of the NO₂/airmixture to an auxiliary conversion reactor depending upon the systemconfiguration and therapy protocols for the recipient. In embodiments,when the delivery system determines the cartridge is almost expired thecomputer may automatically reduce the delivered NO concentration thusproviding users more time to replace the cartridge. This safety featureallows delivery to continue at a reduced rate rather than shutting offcompletely, which could cause rebound pulmonary hypertension.

In various embodiments, a backup delivery system could provide constantflow delivery, proportional delivery to an inspiratory flow signal, orpulsatile delivery to approximate a proportional delivery system. Inembodiments, the backup delivery system may be electronic or pneumatic.The backup delivery system may be designed to support manual ventilation(with an Ambu® bag). The backup delivery system may incorporate air orO₂ delivery for manual ventilation. In embodiments, the backup deliverysystem may be manually activated or electronically activated by theprimary delivery system in a fail-over state. The backup delivery systemmay interface to the same cartridge converter systems as the primary orto a separate set. In various embodiments, the backup system cartridgeconverters may contain the same safety mechanisms as described for theprimary delivery system in this application

In various embodiments, a connector at an inlet end of the conversioncartridge and/or a connector at an outlet end of the conversioncartridge may be polarized or keyed in a manner that prevents thecartridge from being installed in a NO delivery system with an incorrectorientation (i.e., backwards). In various embodiments, different lots ofmanufactured conversion cartridges may be assembled with different setsof polarized or keyed connectors that prevent two cartridges from thesame manufacturing batch from being installed as a redundant set ofcartridges.

The flow meter and voltmeter and/or ammeter provides a means formonitoring the functioning of the conversion reactor and determining alifetime of the conversion media.

The determined value for the characterized conversion reactor can bestored in a suitable non-volatile memory device or other non-transitorycomputer readable medium (e.g., 1-or 2-D bar codes) provided with orattached to the characterized reactor, or stored in the non-volatilememory of a microprocessor-based system. In an embodiment, the flowmeter may be in electronic communication with the microprocessor-basedsystem, and communicate real time measured values from a flow meter tothe microprocessor-based system for determination of the remaining lifeof the reactor and the occurrence of a theoretical breakthrough. Thebreakthrough is referred to as theoretical because it is based upon thecalculated value including the safety factor, so the threshold valueshould be reached before any actual breakthrough of NO₂ occurs.

Characterization of reactors can be accomplished by testing astatistical sampling of each manufactured batch of reactors to failure,averaging the volume of NO₂ converted to NO before reaching abreakthrough limit or consumable reactant exhaustion, and applying asuitable safety factor to adjust for both the statistical dispersionand/or variation of the measurements and variability in component andmanufacturing tolerances, as well as an applicable additional safetymargin to allow for example time to reach a reactor and perform thenecessary replacement before actual breakthrough would occur.

It is to be understood that the present invention is not limited to thedetails of construction or process steps set forth in the abovedescription. The invention is capable of other embodiments and of beingpracticed or being carried out in various ways.

Various exemplary embodiments of the present invention are described inmore detail with reference to the figures. It should be understood thatthese drawings only illustrate some of the embodiments, and do notrepresent the full scope of the present invention for which referenceshould be made to the accompanying claims.

Various exemplary embodiments of the present invention can be used todeliver therapeutic gas to patients suffering from chronic obstructivepulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), andpulmonary hypertension (PH), cystic fibrosis (CF), to name a few. Attimes, the name of a specific disease may not be provided; however, thisis merely for ease.

Although the disclosure herein has been described with reference toparticular embodiments, it is to be understood that these embodimentsare merely illustrative of the principles and applications of thepresent invention. It will be apparent to those skilled in the art thatvarious modifications and variations can be made to the devices,systems, and methods of the present invention without departing from thespirit and scope of the present invention. Thus, it is intended that thepresent invention include modifications and variations that are withinthe scope of the appended claims and their equivalents.

Reference throughout this specification to “one embodiment,” “certainembodiments,” “one or more embodiments” or “an embodiment” means that aparticular feature, structure, material, or characteristic described inconnection with the embodiment is included in at least one embodiment ofthe present invention. Thus, the appearances of the phrases such as “inone or more embodiments,” “in certain embodiments,” “in one embodiment”or “in an embodiment” in various places throughout this specificationare not necessarily referring to the same embodiment of the presentinvention. Furthermore, the particular features, structures, materials,or characteristics may be combined in any suitable manner in one or moreembodiments.

What is claimed is:
 1. A reactor cartridge for converting NO₂ to NO,comprising: an outer reactor shell; an inlet end wall that seals theinlet end of the reactor; an outlet end wall that seals the outlet endof the reactor to form an internal volume within the reactor cartridge;an inlet that facilitates connection of the reactor cartridge to a firstgas conduit and allows passage of gas through the inlet end wall to theinternal volume; an outlet that facilitates connection of the reactorcartridge to a second gas conduit and allows passage of gas through theoutlet end wall to exit the reactor cartridge; a consumable conversionmedia retained within the internal volume of the reactor cartridge thatfacilitates conversion of an incoming NO₂ gas delivered to the inlet toan outgoing NO gas exiting at the outlet; a back end retainer positionedtowards the outlet of the reactor cartridge to prevent consumableconversion media from exiting the internal volume of the reactorcartridge through the outlet; a front end retainer positioned towardsthe inlet of the reactor cartridge to prevent consumable conversionmedia from exiting the internal volume of the reactor cartridge throughthe inlet, wherein the consumable conversion media is retained betweenthe front end retainer and the back end retainer; and a force-applyingmember positioned between the inlet end wall and the front end retainerto apply a pressure to the consumable conversion media.
 2. The reactorcartridge of claim 1, which further comprises a memory chip affixed tothe outer reactor shell, wherein the memory chip stores data relating tothe conversion cartridge that the chip is affixed to on a non-transientcomputer readable medium.
 3. The reactor cartridge of claim 2, whereinthe stored data includes identification data, testing data, and/orcartridge life data.
 4. The reactor cartridge of claim 1, which furthercomprises an impact sensor affixed to and/or operatively associated withthe reactor cartridge, wherein the impact sensor is configured todetermine the number of impacts and/or the severity of the impact(s)experienced by the reactor cartridge. The reactor cartridge of claim 1,which further comprises an inlet with a keyed or polarized cartridgeconnector and/or an outlet with a keyed or polarized cartridgeconnector, wherein the keyed or polarized inlet and/or outlet connectorsinteract with a mechanical interlock to ensure the reactor cartridge isinstalled with the correct orientation in a gas delivery system.
 6. Amethod of testing reactor cartridges to determine an expected lifetime,comprising: assembling a number of reactor cartridges, comprising;providing a plurality of conversion cartridge shells; placing a firstretainer on a support within the shell to partition off a section of theinternal space; introducing a volume of a consumable conversion mediainto at least a portion of the internal volume of the conversioncartridge; placing a second retainer within the shell, that is held inposition against the volume of consumable conversion media by aforce-applying member; closing an inlet end of the conversion cartridgeshell with an inlet end wall, wherein an end of the force-applyingmember is in contact with the inlet end wall and an opposite end of theforce-applying member is in contact with the second retainer, so that aforce is applied to the volume of a consumable conversion media; andclosing an outlet end of the conversion cartridge shell with an outletend wall; randomly selecting a number of reactor cartridges from theplurality of assembled reactor cartridges, where the number ofcartridges selected for testing is less than the number of cartridgesassembled; installing a randomly selected reactor cartridge into a NOgas delivery system; testing the installed reactor cartridge by aprocess comprising: flowing a gas containing a predeterminedconcentration of NO_(S) through the installed reactor cartridge;measuring the amount of NO₂-containing gas fed into the reactorcartridge with a flow meter; detecting the presence of NO₂ at the outletof the reactor cartridge; and calculating the amount of NO₂ converted toNO by the reactor cartridge up to the time NO₂ was detected at theoutlet of the of the reactor cartridge with a computer; and replacingthe installed reactor cartridge with a subsequent randomly selectedcartridge and repeating the testing process until all randomly selectedreactor cartridges have been tested.
 7. The method of testing reactorcartridges of claim 6, which further comprises: calculating the amountof consumable conversion media used up to convert the amount of NO₂converted to NO; averaging the calculated amount of consumableconversion media used up for each tested reactor cartridge; calculatingthe average amount of NO, that would be converted to NO for the untestedplurality of assembled conversion cartridges.
 8. The method of testingreactor cartridges of claim 7, which further comprises: affixing amemory chip comprising a non-transient computer readable medium, andconfigured to communicate with a computer, to each of the conversioncartridge shells; and storing the average amount of NO, that would beconverted to NO on the non-transient computer readable medium.
 9. Themethod of testing reactor cartridges of claim 6, which furthercomprises: measuring the amount of H₂O present in the consumableconversion media with a H₂O sensor, and comparing the measured amount ofH₂O against a predetermined acceptable range for the reactor cartridge.10. The method of testing reactor cartridges of claim 6, which furthercomprises: measuring the differential gas pressure across the consumableconversion media to determine if there is a low pressure differentialdue to channeling or a crack in the conversion media.